Objective: The association between hypoparathyroidism and central diabetes insipidus (CDI) is rare. We report two siblings with hypoparathyroidism and CDI in one of them.
Two siblings who presented with hypocalcemic seizure at the age of 2-yr-2-mo (boy) and 2-yr-4-mo (girl) were diagnosed with hypoparathyroidism. At the age of 3 years, the girl developed central diabetes insipidus with good response to desmopressin acetate treatment. The family history was unremarkable, there was no consanguinity between the parents. The father is of Iraqi/Egyptian Jewish origin and the mother is of Iranian/Romanian Jewish origin. Sequence analysis of the candidate genes for isolated hypoparathyroidism encoding calcium sensing receptor, parathyroid hormone and glial cells missing homolog B did not reveal mutations. Whole exome sequencing identified a homozygous mutation in the autoimmune regulatory gene (AIRE), c.374A>G;p.Y85C, characteristic for Jewish Iranians with autoimmune polyendocrine syndrome type 1 (APS1), which was confirmed by Sanger sequencing. Antibodies against adrenal, pancreatic islet cell, ovary, thyroid, pituitary, celiac, and parietal cell were negative in both siblings, while anti-diuretic hormone antibodies were positive only in the girl. No other symptoms or signs of APS1 developed during 12 years of follow-up. Conclusion: APS1 should be part of the differential diagnosis in children presenting with isolated hypoparathyroidism or hypoparathyroidism with CDI. This case shows that the characteristic Iranian Jews AIRE mutation can also be found in non-Iranian Jews.
